We have a mashup episode today, exploring heart health during menopause and the benefits of hormone replacement therapy.
In this episode, Dr. Felice Gersh dives into the role of estrogen in immune function, inflammation, and heart health. Dr. Deb Matthew highlights the importance of assessing cardiovascular risks and hormone balance in perimenopausal and menopausal women to optimize heart health and minimize reliance on statins.
Join us as Dr. Matthew and Dr. Gersh share their insights on heart health, hormones, and menopause.
[00:01:53] Dr. Gersh guides listeners in understanding and appreciating the impact of estrogen on immune function, inflammation, and the healing processes within the body.
[49:33] Estradiol is vital for heart health, and its decline after menopause can lead to issues like stiffening of the heart, heart failure, and arrhythmias in women.
[00:01:30] Most women fear breast cancer more than heart disease, even though cardiovascular disease is the leading cause of death in women. Yet, clinicians fail to talk enough about the effectiveness of hormone replacement therapy in mitigating the risk of heart disease during perimenopause and menopause.
[00:04:04] While estrogen can benefit the cardiovascular health of women, the risks associated with oral estrogen and synthetic forms, including blood clots and artery plaque instability, have led to hesitancy in using hormone replacement therapy despite its potential long-term benefits when administered correctly.
[00:11:26] The balance of hormones like testosterone, DHEA, and cortisol plays a crucial role in cardiovascular health. Imbalances, such as flat cortisol patterns due to stress, potentially increase the risk of heart disease. Dr. Matthew uses tests like coronary artery scans and coronary intima-media thickness to assess cardiovascular risk in patients before considering hormone replacement therapy.
[00:20:22] Dr. Matthew emphasizes the importance of advanced lipid testing, addressing the nuances of cholesterol particle size and inflammation, balancing hormones, and optimizing thyroid and blood sugar levels to manage cardiovascular risk instead of immediately resorting to statins.
Bio: Dr. Deb Matthew
Dr. Deb Matthew MD, The Happy Hormones Doctor, is a best-selling author, international speaker, educator, wife, and mom of four boys. After suffering for years from fatigue and irritability due to hormone imbalances, her quest to resolve her personal health led her to change everything about her practice of medicine. She has been featured on national podcasts, radio, and broadcast shows, including NBC, ABC, CBS, and FOX. Her books, This Is NOT Normal! and Why Can't I Keep Up Anymore? address hormone health in women and men.
Bio: Dr. Felice Gersh
Dr. Felice Gersh is a multi-award-winning physician with dual board certification in OB-GYN and Integrative Medicine. She is also a recognized expert on PCOS.
“Every aspect of the cardiovascular system is incredibly impacted by female hormones.”
-Dr. Felice Gersh
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Connect with Dr. Felice Gersh
On her website: Integrative Medical Group of Irvine
Connect with Dr. Deb Matthew
Transcript:
Cynthia Thurlow: [00:00:02] Welcome to Everyday Wellness Podcast. I'm your host, Nurse Practitioner Cynthia Thurlow. This podcast is designed to educate, empower and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives.
[00:00:29] February is Heart Month and I could not think of a better theme to use compiling some of my favorite podcasts that I've done with experts with regard to heart health. As many of you know, I spent over 16 years as a nurse practitioner in cardiology and it is a near and dear subject to me. And when you look at current statistics that run the gamut with regard to cardiovascular disease in women, heart disease causes 1 in 32 deaths each year and remains the number one killer of women, approximately accounting for one death every 80 seconds. We know that women present differently than men and by the time women get a diagnosis of cardiovascular disease, they typically have more severe disease than men do. 64% of women versus 50% of men who die suddenly of heart disease have no previous symptoms.
And pathophysiologically, the incidence of heart disease in women lags behind men by about 10 years, and the incidence of heart attacks or myocardial infarcts and sudden cardiac death in women lags behind men by 20 years.
[00:01:39] We know that a great deal of the delay in onset of these symptoms is related to the cardioprotective effects of estrogen, which women, as they make that transition from perimenopause and menopause, become much more susceptible to heart disease. So, today, I humbly share with you a compilation. This is the first of two series, a podcast with Dr. Felice Gersh, Dr. Deb Matthews, Dr. Hussey and Dr. Tom Dayspring. Again, this will be divided over two podcasts because it is quite lengthy but particularly relevant given its heart month and why I want to bring greater awareness to the number one killer of women, heart disease.
[00:02:25] I know you will enjoy this conversation and hopefully to have some actionable steps that you can take, that you can discuss with your internist, your primary care provider, to help with risk stratification and to help identify if there are any areas that you need to tighten up on in terms of lifestyle.
[music]
[00:02:46] Let's jump right in because this is the number one killer of women. There's one death for women every 80 s from cardiovascular disease. There's not enough focus and attention on this, especially in this very special time in our lives in menopause when we're no longer fertile. But this loss of estrogen, unless it's being replaced, has profound catastrophic impact on our health. So, from your clinical experience, when you're talking to women that are in perimenopause, navigating that transition into menopause, I'm sure that cardiovascular risk probably comes into the conversation because you're such a diligent and thoughtful provider. But I thought it would be interesting for listeners to fully understand and appreciate how much estrogen impacts, immune function, inflammatory response, healing in the body, etc.
Dr. Felice Gersh: [00:03:36] Well, that is for sure, in every single aspect of the cardiovascular system. And you mentioned a whole bunch of them right then, is heavily, I mean, incredibly impacted by female hormones. And it is so poorly acknowledged that is the case. And it's really very simple when you think about why that would be. It really comes down to survival of the species and reproductive success. So, once you acknowledge whether you want to have babies, I keep thinking I'm like the ultimate feminist. [Cynthia laughs] I totally want women to control their reproductive destiny, have babies when and if they want them. But whether you want them or not, you need to understand basic physiology of the female 101, which is the female body evolved for the purpose of reproductive success.
[00:04:30] In a human, that means being able to be fertile, to get pregnant and carry the pregnancy to term without complications for mother or for the fetus and then to be able to nurse that baby for at least a couple of years, going back to early times, and then be able to survive to raise that child and several others to do this repetitively, to raise at least a couple of children to survive to their own sexual maturity. And so, to that end, you need to have robust, healthy organ systems of every type. And for sure, the cardiovascular system is critical. When you just recognize even one little fact, which is that the placenta has to have incredible vascularity and blood flow and the ability to deliver all the nutrients and oxygen.
[00:05:24] You need to be able to pump at least 50% more blood volume around the body when you're pregnant. So, you have to have a very energetic heart. And that is not really well understood even by cardiologists. And you need to have a vascular system that can be able to improve its state of being in order to create new blood vessels, angiogenesis, so that you can perfuse all the areas of the body on a growing uterus. And it's so amazing, the whole state of pregnancy and how involved the cardiovascular system has to be. And then you end up having the master hormone estradiol, and that has to be coordinating all the organ systems to work together to keep that pregnant woman and the fertile woman healthy and going for many years.
[00:06:12] So, nature though, has sort of an end stop time, and that's called the menopausal transition, when fertility declines and then is gone. And our beautiful life hormones from the ovary, and though we have the top of the heap is the estradiol and then it's sidekick progesterone and testosterone is a separate issue because that's really-- more of that is produced directly or indirectly by the adrenal glands. So, that's a topic for another day. But when you lose those vital life hormones and your fertility goes away, it's really important for every woman to realize this is a huge metabolic transition and not for the better. No matter how healthy a woman is, no matter how hard she tries to do everything right with her lifestyle, she cannot spontaneously get healthier because she goes through menopause.
[00:07:07] Because those vital life hormones are sustaining every organ system and especially the cardiovascular system, which is the highway of the body, producing the ability to supply every organ system with oxygen and nutrients and for the immune system to circulate and then be able to help deal with injuries, trauma, dead cells, infections and so on. And of course, to perfuse that vital organ, the brain, and to take the impurities away and maintain a healthy blood-brain barrier so you don't have what we call like leaky brain and so on. So, it's just an incredible loss of metabolic homeostasis. And when you go detail by detail, which we can do, looking at like the specifics of what does estradiol do in the various parts and so on of the cardiovascular system, it is shocking.
[00:08:04] Like we were chatting before, we started about how so many women and their medical providers don't realize this huge shift in the ability of the body to optimize everything, including the cardiovascular system with the transition into menopause.
Cynthia Thurlow: [00:08:20] What are some of the risk factors when you're doing a history? Maybe you have a new patient, someone comes to you. What are some of the harbingers of concern for you in terms of cardiovascular disease risk in younger women as they make that transition? Because I recently interviewed Dr. Tom Dayspring and he was identifying, these are things that I will lean into if a young woman mentioned she has a history of preeclampsia or gestational diabetes, things that will put people at greater risk for developing vascular issues as they get older.
Dr. Felice Gersh: [00:08:54] Well, we'll go into that in a moment. And just to say, as an OB/GYN, I delivered thousands of babies. This was so evident to me decades ago. But this is only now just coming out as oh, risk factors, including pregnancy-related complications. It's like, where have you been, guys? Like, you obviously ignored everything is involving obstetrics because this was so evident. And it's like giant duh. So, the biggest stress test of a female is pregnancy.
[00:09:24] Now everyone knows a stress test. You get on the treadmill, you have an-- echo, and you put the body under some stress, make them run or you inject something that creates a stress and then you see the response of the heart and you see if there are issues and they're like I said, “When you are pregnant, you have to pump at least 50% more blood. It is a huge stress on the heart. If you don't have a healthy cardiovascular system, then you are going to fail your stress test of pregnancy.” And basically, when you are pregnant, you become mildly insulin resistant and there's a purpose to that.
[00:10:01] When you are pregnant, you develop almost immediately leaky gut. Now we say, “Oh my God, how can you get leaky gut?” It's because it's a mechanism. That's why only really healthy people should be pregnant and that's why only young people are supposed to be pregnant. And the older you are, the higher risk you are. I mean, we've known that in obstetrics forever, a pregnant 40-year-old has a much higher risk potential than a healthy 25-year-old. So, when you look at what is happening in a pregnancy with insulin resistance, like you mentioned, gestational diabetes. Well, how do you get fat quickly if you're pregnant in ancient times when there wasn't food at every corner. Well, the way that it happened is nature would make you mildly insulin resistant. And what does that mean? It means that the insulin you're producing is less effective. So, you're going to then have your pancreas make more of the insulin.
[00:11:00] So, insulin is the hormone that really encourages the production and storage of fat. That's why pregnant women can eat very little more, sometimes not eat more at all, and they still gain weight because of this inherent insulin resistance status which is created by a leaky gut. That's why when you're not pregnant, you don't want to have leaky gut, among many other reasons. So, you end up having higher glucose levels in your blood and you'll have higher insulin. And the higher glucose in the blood is necessary because it passes through the placenta into the baby so that you can grow that baby in a relatively short amount of time to get a healthy baby. So, you have this amazing system. But everything is like on thin ice in pregnancy.
[00:11:45] If you don't have good metabolic health going in, then that mild state of insulin resistance turns into full blown gestational diabetes. That's why gestational diabetes is a thing. And women could have no sign of diabetes prior to pregnancy, and then it seems to like resolve afterwards. But that underlying metabolic, we'll say, sort of dark clouds hanging over that woman, they're still there and then what happens? They're being okay as long as they have their ovarian function. That magical hormone estradiol, which optimizes glucose transport, it helps maintain proper insulin function. It's just the metabolic homeostasis hormone. So, when you lose that you lose that one thing that was keeping you on track. And that's why when you go through the menopausal transition, women who previously had gestational diabetes have enormously higher risk of developing regular, garden variety, unfortunately, very unhealthy type 2 diabetes.
[00:12:57] What about preeclampsia or gestational hypertension? Well, if you do not have the healthiest state of metabolic health going into pregnancy, when you're pregnant, you have to then create all these new blood vessels and you have all these dynamics happening with the placenta and you have to be able to deal with all of that. If you have any borderline state of metabolic health, then you may have problems with gestational hypertension and preeclampsia, which is really heavily a vascular disease. And then once again, when you lose your estradiol with the onset of menopausal transition, and then thereafter, you will have a much higher potential to develop hypertension.
[00:13:44] And in fact, even without that history, by age 65, as a general statement, 75% of women will develop hypertension or at least they're on the track for prehypertension, which is a thing now, recognizing that's like the early stages, prediabetes to diabetes. But these so-called preconditions are not like okay status, they're actually bad status. Things are really happening that are harmful. So, we can then use pregnancy as sort of a bellwether of what will happen later in terms of that sort of those problems. But what else, in addition to pregnancy, there is irregular cycles. So, we now know that women who've had any kind of infertility, and if they've had irregular cycles then they also, and of course the poster child for that is of course polycystic ovary syndrome.
[00:14:44] They will have a much higher risk of having these metabolic dysfunctions as a transition into menopause. So, basically in now the gynecological world it is acknowledged, although not necessarily actually acknowledged in a sense that you do something about it. It's written that fertility is a vital sign. Now, what is a vital sign like your blood pressure, your pulse, your temperature. So, fertility is a vital sign. If you are of the reproductive age and you're a female and you are infertile, you are having any sign, even if you're not trying to get pregnant, you have all the signs of being infertile. Like no periods, irregular periods. Then that is a big bright red light going off saying this individual has metabolic dysfunction. That's why it drives me crazy. If you just treat them with birth control pills like it's like a cover up.
[00:15:44] And that's another risk factor that is totally under acknowledged, young women, and the data only goes to teenagers, like anyone under the age of 20. And that doesn't mean, if you're 21, it's okay. It just means we have no data. And what am I talking about, I'm talking about use of oral contraceptives or similar that women who are started on them prior to the age of 20 have an increased lifetime risk of cardiovascular events. That's like a big deal because now it is considered in the conventional medical world, okay, to start any girl, and these are girls, any girl on oral contraceptives, as long as you are one year out from her first period, that's it. And we have girls who are starting their periods way too young. Like they could be 9, they could be 10.
[00:16:35] That's how you could have the case of a ten-year-old getting raped and getting pregnant. It's like who could get pregnant when you're 10 years old, they're starting their periods at age 9 that's another thing we'll mention as a risk factor. Early onset of puberty is another risk factor for cardiovascular death or events later on when you lose your hormones, because that is not a good thing to start your period so early. But for girls who do start their period early or whatever the age it is, once they're out 12 months from their first period, if they have acne, if they have irregular cycles, if they have cramps by the way, in terms of cycle problems, it's not just irregular, it's like PMS, it's like really heavy, it's like really painful.
[00:17:18] Those are all in the category of abnormal cycles in some form or fashion. So, any girl who is in that category or sometimes they just say, “I don't want a period.” So, the moment moms doesn't know, she doesn't know, she says, “Okay, put my 13-year-old daughter on birth control pills” because she thinks, well, I mean, regulating, regulating their periods. And this way if they're in sports, they don't have their period when they're in competition. I mean, I get where they're liking that concept, but unfortunately, you're affecting basic metabolic functions in a way that is harmful. Whether we like it or not, you just have to tell the truth about that.
[00:17:54] So, if you're started on these oral contraceptives or similars, patches, rings, and you're started at young ages, it actually has an impact on cardiovascular risk for the rest of that person's life. And like I said, it's not that if you start when you're 20 or 21 or 22, you know that there's no risk. We just have no data. And the reason we have no data is because 90% of American females are on some form of hormonal contraceptives by the time they get into their 20s. So, there's no control group who are you comparing against? They're all in that category. So that makes it almost impossible to then backtrack and see, well, is there an increased risk? It's like everybody.
[00:18:36] So, it doesn't look like there's an increased risk, but it's a problem because as you mentioned, just at the get go, cardiovascular events, heart attacks, strokes are the number one killer of women out doing virtually everything else combined. That's like how big a deal it is. And it would be okay if you said, “Well, look, everyone has to die.” If you die of a [Cynthia laughs] heart attack in your sleep when you're 100, that's okay. But we're talking that a very significant percentage are younger women and often in their prime. And if you have any of these precursor risk factors, everything gets bumped up by a decade. Another risk factor that doesn't really get its fair share of attention is early onset of menopause. That is a big deal.
[00:19:25] And it's so shocking when you think, well, if you start your menopause at an early age and if we look at what menopause categories are, so normal is considered 45 to 55. So that's a whole decade right there that's considered normal. And the definition of menopause, which is totally arbitrary, is 12 consecutive months without any vaginal bleeding. And I say vaginal bleeding because if you go nine months and you have no bleeding and suddenly you start spotting or bleeding, the last thing as an OB/GYN that I would assume is that after nine months you spontaneously ovulated. I would call that abnormal bleeding until proven otherwise. So, I mean, we don't know what that is. We don't know what that bleeding means.
[00:20:06] And in fact, when they talk about late onset of menopause is a risk factor, it's like, “Hey you guys, that's because you have a crazy definition of menopause. You're saying any bleeding start from square one again. If you go nine months and then you start having spotting, that means the clock starts over again. And then you wait another nine months and then you have some more little bleeding and the clock starts over again. So, they say, “Well, if you have late onset of menopause, that's a risk factor.” But that's because these women aren't actually ovulating. These are not normal cycles. This is dysfunctional uterine bleeding or it could be even worse. It could be endometrial hyperplasia, adenomatous or precancer or even endometrial adenocarcinoma. We don't know what that bleeding is if you don't investigate it.
[00:20:54] But that's not like you're still ovulating. [laughs] But they call that late menopause. That's not late menopause. That's ongoing abnormal bleeding that's going on for years and needs to be evaluated and needs to be addressed. But they'll put that into that category. That's why that is nonsense. If a woman has normal cycles and she has a later onset of menopause, that's a good thing. Not if she has random bleeding going on sporadically for years. So, the normal menopause is supposedly 45 to 55, and that's when you actually have no more periods. So, late menopause is over 55, early is 40 right up to 45, and premature is prior to 40. The earlier you lose your ovarian function, the worse off you are. And that is proven without a shadow of a doubt. These are life giving supporting hormones.
[00:21:51] And so it is a risk factor for earlier onset of every cardiometabolic. So, we put that together, cardiometabolic. So, metabolic would be things like obesity and diabetes and all the unbelievable risk factors that come along like kidney disease and so on, that are part and parcel of diabetes. And it's when you actually break it down. Well, what does estradiol do? We talked about cholesterol. Well, it has a huge role in the liver production of cholesterol, where 90% of the cholesterol circulating in the body comes from liver produced cholesterol, only 10% is from diet. And then if we look at, the liver and the production of cholesterol and the recycling of cholesterol, all of that is under the control of estradiol.
[00:22:42] And then if you look at just every aspect of vascular health, everything all under control. And I had a paper published about not even a year and a half ago that was in Mayo Clinic proceedings on the renin angiotensin aldosterone system, which most doctors, even cardiologists think it's evil. They think down with that system. [laughs] It gives you high blood pressure. And we have a lot of pharmaceuticals that are addressed at modulating that system. You may have heard of some of them like ACE inhibitors and the ARBs, the angiotensin receptor blocker drugs. So, these are things like-- lisinopril is an ACE inhibitor and losartan is an ARB. So, these are really common drugs and they are modulating this RAAS system, the renin angiotensin aldosterone system. Estradiol is the master regulator of this system.
[00:23:35] And this system has two branches, an anti and a proinflammatory branch each and without estradiol it defaults into the proinflammatory branch and that causes vasoconstriction because it's a life-saving system that's really designed to modulate how the body responds to a stress like an infection trying to take hold in you or an injury from trauma. And if you just think about it, if you are in an injury situation and you have a big laceration, your body is going to want to constrict your arteries so that you don't develop hypovolemic shock. So, you want to maintain your blood pressure so you don't die from shock. And then you're going to want to clot because you want to stop that bleeding.
[00:24:32] So, you're going to aggregate your platelets and activate them to create clotting and then you're going to want to activate your immune system. Because you don't want infection bacteria to come into that wound. So, you're going to activate your immune system to go and run to the scene of the injury to start exploding with their inflammatory cytokines to kill any invading pathogens that are trying to get in. And that's like the proinflammatory stage when you don't have enough estradiol, you stay in that situation so you have vasoconstriction and your platelets are in a more pro-clotting situation and your immune cells are in an active proinflammatory state of creating inflammation even when there is no invading pathogen and there is no damaged tissue that needs to be addressed.
[00:25:26] And then the estradiol not only institutes that inflammation, but it also goes into the off switch so that you go into the healing resolution. So, you have growth factors, healing factors. You can create new blood vessels, new tissue. All of that is under the control of estradiol. And in the normal state when you're not injured, when you don't have a pathogen trying to invade you, you are in the calm anti-inflammatory RAAS system where the blood vessels are dilated and you don't have constriction, so you don't have high blood pressure, your platelets are not activated, you don't spontaneously clot, you don't have activated immune cells, so they're not creating the inflammatory response anywhere in the body.
[00:26:09] And you're healing and maintaining all of your tissues because you're in that maintenance state where everything is being surveilled and maintained in a good calm state. So, it gets so confusing even to doctors because they don't understand that in order for this system, this RAAS system which is so critical for survival, to be properly modulated and not be in the default proinflammatory state in that whole pathway, you need to have estradiol. And they get mixed up. Because when women go on birth control pills, for example, or they're given like in the Women's Health Initiative, conjugated equine estrogens that are given orally, those types of estrogens are different from estradiol.
[00:26:56] Well, the birth control pill, estrogen, ethinylestradiol is technically an endocrine disruptor or a xenoestrogen. And conjugated equine estrogens, when given orally, contains a whole array of different things that you would never even have in a human body. But both of them primarily will turn into estrone, which is a different type of estrogen. So, it's important to understand that estrogen is not a hormone. It's a family of hormones. And just like B vitamins, there's not a B vitamin. There's a vitamin that has a big letter B and then a number and then a word that goes with it like B1 is thiamine, B12 is cobalamin. Well, estrogen has a big letter E and then a one, a two or a three, there's a four, but that's a fetal estrogen. We won't go there. And the two, E2 is estradiol. That's the one that the ovaries make. E3 is estriol, that's the dominant one of pregnancy that the placenta makes, which creates a whole different scenario of your immune system and leaky gut. You don't want to try to recreate pregnancy in a nonpregnant woman, not that you could anyway. But that is never our goal. That's nonsensical. And E1 is estrone, which is in balance with estradiol in a normal healthy reproductive female as the body needs it.
[00:28:17] But those other estrogens from the Women's Health Initiative and in birth control pills, they turn primarily into estrone. Estrone acts on one receptor and estradiol works on all the receptors for estrogen in a balanced way. And if you think of it in sort of simplistic terms, E1 operates the receptor that is on immune cells called innate immune cells. They're the primary first responders if you have an injury or an infection. So, you're turning on the switch for the immune system to be in an activated proinflammatory state when you have predominantly E1 in the body. And that is a problem. [laughs] And that also is the estrogen that is made in fat tissue under an inflammatory state, which is what happens to women after menopause because they go into that proinflammatory state which some clever person termed inflammaging. But it's only that proinflammatory state because you don't have the balanced estradiol and you go down that default pathway into only the proinflammatory and it's fed by inflammation, even causing more estrone being produced by the transformation of adrenal androgens.
[00:29:41] They're male type hormones, but women have them too. And the bulk of them come from the adrenal gland and they're like DHEA, DHEAS, you may have heard of those. And they get converted into estrone. And there is an enzyme that can convert estrone to estradiol. But when you have a lot of inflammation, that enzyme is downregulated, so it works less well. So, you get stuck into producing all this estrone and it's stuck as estrone, which turns the on switch for inflammation. So, you're in this proinflammatory state that's gets the snowball effect because you then have more inflammation which then causes more of this estrone. But that is not the same as having estradiol from your ovary. And doctors don't seem to get it. It's not that hard. It's not rocket science that you have different estrogens, they have different effects, and if you have the wrong one, you get an imbalance of how the immune system is responding. And people know this with fats. That's another like, good analogy. If you have someone who's eating lots of processed food and it contains a lot of trans fat, which you're not even supposed to have, but put into these foods, it's also converted from processed oils and stuff. You can actually, not intentionally, but it turns into trans-fat.
[00:31:03] But when you made, they used to put trans-fat in on purpose. So, these were very bad for people. Trans fat is very bad. So, you wouldn't say never have food with fat, although they did say that, but that was wrong. [Cynthia laughs] Never eat food with fat because fat is evil. Well, trans fat is evil, but Omega 3 and the monounsaturated fatty acids from olives and the best type of olive oil, and if you have walnuts that are nice and fresh, you have to have fat, from avocado, they're called them, essential fatty acids. You have to have fat in your body to survive. And so, you cannot equate evil trans-fat with these healthy essential fats, but that's what they did to poor estradiol. It's like the evil twin. And you have these other estrogens that would never even be in a human body, like ethinyl estradiol from a birth control pill or the horse urine product that would never be in a human body. And you put it into it, dry it, put in a tablet, and then take all the bad stuff that happens and then you put it on the poor estradiol. [laughs]
[00:32:12] And then women don't get proper treatment and they learn to fear their own beautiful hormones. It's so simple once you just get down to it and you look at all the amazing things that estradiol does throughout the cardiovascular system with the enzyme systems that it controls. If you're interested, we can go into all the different enzyme systems, which are fascinating, that are all modulated and not just the ones that are in the pathways of the RAAS system. It's a whole slew of other ones as well.
[00:32:41] But once you understand that fertility is a vital sign, that nature made it so that women would be optimally healthy during the reproductive years, and that estradiol is the master of everything that has to do with on/off for inflammation and vascular health and heart health, the myocardium, the conduction system of the heart, so you don't have palpitations and atrial fibrillation, which is now rampant after menopause. All these things are under the umbrella control of estradiol. And when you lose it, you lose all the controls of these systems. And so, if we just think of menopause as what it is, it's really simple. It's a hormone deficiency state. And we treat it like any other hormone deficiency state.
[00:33:28] If you don't have thyroid because you had to have your thyroid gland removed or you get Hashimoto's and you're not making thyroid properly, nobody would say, “Eh, whatever, just eat more vegetables or just suck it up.” [laughs]
Cynthia Thurlow: [00:33:45] So, interesting the way that things have evolved since the WHI and something that I want to make sure we definitely touch on before we end our conversation is talking specifically about things in cardiology, I saw a lot of patients with heart failure, diastolic dysfunction. So, when we talk about the heart cycle, our heart fills in systole and then gets pumped out of the left ventricle and then diastole is when, it's this passive, passive filling of blood in the heart. And it's very common to see this in older patients. And so, I was fascinated when I was preparing for our conversation, realizing that, changes in sex hormones specific to estradiol actually leads to diastolic dysfunction.
[00:34:29] So, you get the stiff ventricle-- this is oftentimes where you'll see-- In many instances, people will develop heart failure related to diastolic dysfunction. But let's talk about some of the changes that go on. I know we've alluded to some of them, but I think for many people this will make it sound a bit more tangible.
Dr. Felice Gersh: [00:34:49] Let me just do a very quick overview of the different ways that estradiol directly affects the cardiovascular structures. So, if we look at the arteries, so in order for an artery to be healthy, you have to have a healthy lining called the intima. Well, estradiol is the key on switch for an enzyme called endothelial nitric oxide synthase, which causes the production of nitric oxide, which is a gas which we can't measure, but we can indirectly measure it by getting a blood test for ADMA. But nitric oxide is essential for vascular health. It also has many other benefits. It keeps platelets from clumping and clotting. It just maintains the health of antioxidant status so you don't have inflammation which damages everything. So, it maintains vascular dilation so you don't have constriction and hypertension.
[00:35:52] So, nitric oxide is essential for vascular health. And without estradiol you will not have adequate nitric oxide production. And that's a huge problem. And then if we look at prostacyclin. So, prostacyclins also maintain vascular health and keep platelets from clumping. And estradiol once again helps to create these essential prostacyclins and the COX enzyme system. That's what's interfered with when you take an NSAID, a nonsteroidal anti-inflammatory and these COX enzymes come in different numbers. COX-1 is the one that keeps everything wonderful and happy and peaceful. COX-2 is what we would have, that would be instituted if you have an inflammatory state. So, it would be only triggered inflammation.
[00:36:45] And that is the one that is supposed to be knocked down or blocked by the NSAIDs, but they actually block also to some degree COX-1, which is why they are associated. If you take an NSAID for at least three days, you have tripled your risk, especially as you're older, of having a heart attack or stroke. That's why long-term NSAIDs are really counterproductive. They're only good to take very short term, like up to three days. But it turns out that estradiol maintains this whole enzyme system, the COX enzymes, that keeps you in that happy COX-1, except if you need to initiate an inflammatory response because it's modulating that whole inflammatory on/off switch.
[00:37:25] And then if we look at like cholesterol. So, cholesterol will only become problematic if it is oxidized because if it's rancid, we call it oxidized LDL, then it is damaged tissue. Damaged tissue is recognized by the immune cells and then they gobble it up because it's just damaged tissue. So, cholesterol travels around the body in little envelopes called apolipoproteins. If you wrote a check, you can't just drop it in the mailbox. You put in an envelope. You can't drop cholesterol in the blood. It needs an envelope. These are the apolipoproteins. So, these are structures and if the cholesterol gets oxidized or rancid, then it gets gobbled up by the gobblers, the macrophages. And these macrophages are attracted to damaged tissue. If you also have damaged lining, the intima of the artery, they line up along the damaged arteries inside, here's the blood flowing and there are cracks in fissures.
[00:38:24] And these immune cells carrying the oxidized cholesterol work their way in through the cracks and fissures into the actual wall of the artery, where they create even more inflammation and through the signaling agents call it more inflammatory cells, creating basically a pile of junk in your artery wall. And if it's very inflammatory, it can erupt like a pimple popping, okay. And it pops and it goes into where the blood is flowing. And that little hole in the artery that was created by the rupture, a little clot forms on it like a little scab. If you ruptured a pimple, and if that breaks off, it travels downstream. It might as well be a rock at that point. It's not dissolved. It will be like a boulder, and it will block the artery somewhere and that can trigger.
[00:39:05] If it's in the brain, a stroke. If it's in the heart, then it's a heart attack. If it's in the vascular system of the intestines, it's ischemic bowel. So, it's blocking blood flow. So, you're not going to have oxygen downstream and in the heart in women, that will trigger a heart attack and what people die from a heart attack isn't the loss of oxygen to the muscle, killing the muscle that comes later, that causes heart failure. Like you mentioned different types of heart failure, but initially what happens is it triggers an arrhythmia and after menopause, women's system involving maintaining proper rhythm becomes much more fragile, and women will go into a fatal arrhythmia and women die from first heart attacks dramatically higher than men.
[00:39:55] And it doesn't take as much for women to get triggered into a fatal arrhythmia. And it doesn't have to be a big area of the heart that has oxygen obstructed from the blood vessel could be a tiny little one, because it's not about loss of oxygen to large areas of the muscle of the heart. It's just that it triggers this arrhythmia through the electrical conduction system that can be fatal, totally fatal. And so, it turns out that estradiol modulates an enzyme called paraoxonase 1, also known as PON1, that prevents oxidation of cholesterol. That's why premenopausal women have a much lower rate of having plaque form because they have this beautiful enzyme that helps to protect the oxidations of cholesterol. So, it doesn't happen.
[00:40:54] As well, cholesterol goes way up after menopause because the receptors on the liver called LDL receptors, so when you have old cholesterol, it comes back to the liver, and it's carried by these apolipoproteins called A1, so that's also known as reverse cholesterol. They come to the liver and they dock like a spaceship in a docking port, and then they go back into the liver, and then they either get recycled if needed or they go out the bile duct. That's the trash chute into the intestine, where if you have binders, like lots of fiber in your diet, you can poop it out, okay. And that's why things that are very binding like oatmeal, has the little heart from the American Heart Association because it can bind cholesterol in the gut, and then you poop it out.
[00:41:40] So, in order for those receptors on the liver to take back the cholesterol, to get it out of the circulation, you need those receptors working. Well, it turns out estradiol maintains the functionality of the receptors on the liver to pull the cholesterol out of the blood. Without estradiol present, the cholesterol just accumulates in the blood, and then it's subjected to more oxidation potential, because of more inflammation that occurs after menopause in an absence of adequate estradiol. So, you can see how this is just devastating. And then when you have problems, you get leaky gut because you don't have the right estrogen and the right microbiome is related to hormones too. And then when you have inflammation in your gut, it affects your liver. So, now you have inflammation in your liver.
[00:42:25] And after menopause, women have much higher rates of non-alcoholic fatty liver and then you have a dysregulated liver that becomes a factory for glucose and triglycerides, which are fats and cholesterol. The liver is a manufacturing center and it's dysregulated when you have this impaired gut barrier and you have dysbiosis or the wrong microbial population in the gut, which happens virtually to every woman as she goes into menopause. And then you have dysregulated liver and then you have all this glucose and triglycerides and you have all of this cholesterol being spewed out and you can't even get it back out again. So, you can see how this creates cardiometabolic total chaos. And I mentioned glucose regulation is controlled under estradiol. The glucose transport system of how the glucose in the blood gets into the cells is under the control of estradiol.
[00:43:19] Without estradiol, the cells that need the glucose for energy can't even get them. And the mitochondria, now you mentioned about the heart, I mentioned of a woman who's pregnant has to be incredibly more energetic than that of a man. The mitochondria of a woman's heart are special. They are able to produce more energy. In order to do that, you need estradiol. In order to make energy and what's called the electron transport chain, you need to have estradiol. And then as a side effect of creating energy, you have a byproduct that's very toxic called superoxide and it cannot get out of the mitochondria. It's like stuck in the mitochondria unless it's converted into hydrogen peroxide, which can diffuse out of the mitochondria and in the cell be converted into harmless water.
[00:44:07] But that won't happen if you don't have enough estradiol, because the enzyme system that turns superoxide, this toxic waste product caused by the production of energy, needs to have this enzyme to convert it, and that's called manganese superoxide dismutase. That enzyme requires estradiol to work. So, if you don't have estradiol, you're not going to make energy properly. And what energy you do make, it creates this toxic waste product that you can't get converted to get it out of the mitochondria. So, it kills the mitochondria. So, now you have a problem of a poorly energetic heart. This is unique to women, and so it's ignored. And you can see it on an echocardiogram that the heart, when it's relaxing, like you mentioned the diastolic phase. So, the diastolic phase is when blood pressure is lower because the heart is filling, not pumping.
[00:45:05] The pumping part is systolic and that is reflected in the higher pressure, the blood pressure, like 120. And then when it's relaxing and refilling, that's the lower blood pressure because there's nothing coming out of the heart at that time into the blood vessel. So, the pressure goes down, and that would be like 120/80. So, the diastolic part, the filling part, is unique to women in that the heart is, like you mentioned, stiffer because the mitochondria are not functioning properly. And so, it's like you see it on this is a pretend version. So, a normal heart would be pumping smoothly and with diastolic dysfunction, it would be stiffer and so the contraction part is fine. It's the opening when it's refilling that it's stiffer and that is called mild diastolic dysfunction.
[00:45:54] And it can lead to a type of heart failure that's pretty unique to women. That's called heart failure with preserved ejection fraction. In other words, the heart is still pumping the blood out, so that's called preserved ejection fraction, but it's actually a dysfunctional heart big time, because it is not relaxing properly. And that heart can kill you. That kind of heart failure can kill women. Heart failure is not a rare condition. And the cardiologists are not even looking for diastolic dysfunction like that. And even when they see it, they often discount it and say, “Oh, lots of women have that.” Yeah, it's really bad. It's a sure sign that it's an energetic deficient heart. So, these are huge things. And then the whole electrical conduction system that's controlled through the autonomic nervous system is regulated by estradiol.
[00:46:49] The neurotransmitters that cause heart rhythm is all controlled. It's a neurological kind of thing. It's all controlled through estradiol, which is why women are so prone to atrial fibrillation. And they're prone to having supraventricular tachycardias, where they have palpitations and rapid heartbeats. So many women I see, they go to the cardiologist and they're just put on beta blockers, which are drugs that sort of slow the heart rate down, which can be helpful. But it's not addressing the root cause, which is that they're having conduction problems because their autonomic nervous system is dysregulated because they don't have enough estradiol. And so, you can see how there's just such a wide array of issues that come into play and it's fascinating.
[00:47:38] And this is not even covering everything because it's complex and simple at the same time. On a molecular basis, it's really complex when you look at pathways and all of this and that. But when you just look at it's all designed for pregnancy success and reproductive success. And you need to have a strong, energetic heart, you need to have really healthy arteries, you need to be able to create an incredible placenta. You need to have the proper hormones to keep you in the proper time zone, to have proper digestion, all these things need to be optimized for reproductive success when you don't have reproduction any longer because nature deems you too old and too risky and the reproductive capabilities go away, so too do these vital hormones and then you're going to suffer in every organ system and hugely, I mean just hugely in the cardiovascular system.
[00:48:34] And the best ultimate way is to start early in perimenopause like you said, “Wherever you are, it's where you are. You just go and do the best you can wherever you are. I deem it you're never too late.” And that's not the conventional approach. They say if you're out over 60 and you haven't been on hormones or even if you have been and you reach 60, like now, you're too old. That's illogical. That's just like bizarre actually when you think about it, there's nothing that changes between 59 and 61.
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Cynthia Thurlow: [00:49:07] So, in continuance to our last conversation, which was so impactful and so information savvy, today I thought we could shift and talk a little bit about the perimenopause-menopause transition and how women's risk of cardiovascular disease increases significantly. I was just reading a statistic that I want to share with listeners. Cardiovascular disease causes 1 in 3.2 deaths in women each year in the US remains, the number one killer of women, accounting for approximately one death every 80 seconds. Why are we not talking enough about the role of HRT and how this improves not only our all-cause mortality but our cardiovascular risk reduction? I know that you're talking about it, but why are we not talking about it enough as clinicians?
Dr. Deb Matthew: [00:50:00] Well, we, as women are scared of breast cancer. We worry about breast cancer. We lie awake at night being scared of breast cancer. Breast cancer takes women's lives relatively when they're younger sometimes. And so, that is one of our big fears. We don't fear heart disease in quite the same way, do we? Like most of us, if we're in our 40s and our 50s, we're not lying awake at night worrying about having a heart attack, even though that is the way that most of us are ultimately going to meet our end. But heart disease, as a general statement, tends to take women's lives relatively when they're older. And so, we're not so worried about that. But of course, heart disease is something that happens sort of very gradually over many years. And so, we need to be worried about it now. We need to be doing the things that we can do to prevent. So I'm really glad that we're going to be talking about this today because this is so big and women need to know.
Cynthia Thurlow: [00:51:01] To me, the thing that I think is really interesting is this complex interrelationship with estradiol and how that actually protects our vasculature, it protects the internal lining of our blood vessels, the endothelial lining and helping women understand as well as clinicians that we have this 10-year window. And ideally, some people will say a five-year window of when we make this transition into menopause and when we start HRT. But in your clinical experience, do you find and you mentioned this already, we're so worried about breast cancer. We're not thinking about coronary artery disease. But are you seeing an uptick or more awareness around this topic or do you feel like it's still kind of flatlined? We think about men and men dying early of cardiovascular disease, and yet we think of this as like an old person's problem, but it really isn't. It's a now, it's a now issue.
Dr. Deb Matthew: [00:51:56] It is. Well, I think there's so much to talk about. We need to talk about all the ways that estrogen is beneficial for women's hearts. But then we also need to think about why would the cardiologists that you were working with want women to stay away from estrogen and if we sort of unpack that just a little bit, one of the things that we always used to do in the past when we were giving women hormone replacement therapy is we gave it as a pill. And what we learned is that when we give women estrogen orally, especially if we're not giving them the bioidentical form, which is estradiol, which is what our ovaries naturally make. But there's many chemical forms of estrogen that come from horse urine. There's different kinds of estrogen.
[00:52:41] When we give estrogen in a pill, it increases the risk for blood clots, and especially the synthetic estrogens. And we know this whether it's in birth control pills, whether it's in hormone replacement therapy. And so, a blood clot in your heart would be a heart attack or a blood clot in your brain would be a stroke. So, if we're trying to do something to reduce somebody's risk of heart disease, it wouldn't make sense to give them something that's going to increase their risk of a blood clot. So that was one part of it. Another part of it is that when women start on HRT, relatively, when they're older, especially, and when they take this oral estrogen, one of the things that it seems to do is it causes plaque in our arteries to become more unstable.
[00:49:51] So, if you have plaque in your arteries and the studies were done on, it's called conjugated equine estrogen, which is the estrogen that comes from horse urine. We know it as Premarin. It used to be the estrogen that everybody took. So, if we give women Premarin and already they have plaque in their arteries, in the first 12 months of being on Premarin, there was an increased chance that a little piece of plaque would break off from the inside lining of their arteries, become a clot, and therefore they could have a heart attack. Now, if that didn't happen within the first 12 months, the risk of heart disease started to go down and down and down.
[00:54:15] So, the longer that they were on the estrogen, even this kind, that increases the risk for blood clots, the risk for heart disease went down. But all that doctors need to hear is if you take the pill, there's an increase in the chance of a blood clot, an increase in the chance of a heart attack, and they're going to write the whole thing off. And most of the time, if you're a woman going through menopause, you don't even know if you have plaque in your arteries. Nobody's even really started to check for that, for the most part yet, unless you've got other risk factors. It causes blood clots-- It could cause blood clots.
[00:54:49] The blood clot issue is much more of an issue in older women than in younger women. But hormones just get all painted with the same brush. It could make plaque more unstable in the very beginning. And it's probably because the estrogen is doing good things to the plaque. It's changing. It's helping except that maybe a little piece could break off. And that's part of the downside. And then the third thing that went wrong is that we were also giving women a drug form of progesterone. So, instead of giving progesterone like our ovaries make, we were giving women medroxyprogesterone acetate, which is a chemical, a man-made chemical that's meant to mimic progesterone. It was studied for what it does to our uterine lining, and it can protect our uterine lining from the effects of estrogen.
[00:55:36] But we didn't really study what it does everywhere else. And what it did in our heart is it caused something called coronary vasospasm, which means our coronary arteries would go into spasm, they would squeeze down, and then blood couldn't get through, and it was causing essentially a heart attack. So, if we give women a pill that makes their plaque unstable, increases the risk for a blood clot and squeezes their arteries, that's not the greatest way of going about preventing heart disease. And so, in the study, the one that you talked about, that Women's Health Initiative study, the main point of the study was supposed to prove once and for all that hormones were the greatest thing since sliced bread and they were going to reduce heart disease in women but it came out to be a wash.
[00:56:24] It's not that it made more heart disease in women, it just didn't reduce the heart disease the way that we were hoping it would. And it was also done in older women. So, the average age of women in the study was quite a bit past menopause. So, there were just so many things wrong with the analysis, but hormones just all got lumped into the same basket with the message that hormones are potentially bad and dangerous, and they don't, in fact, decrease women's risk for heart disease. And one of my favorite factoids is that we have 10 times more testosterone than estrogen in our body bodies. It's just that men have 10 times more testosterone than women do. But if a woman makes a fair amount of testosterone, that testosterone naturally gets converted into estrogen in all of us.
[00:57:14] That's just a natural thing that happens. So, if somebody who has a generous amount of testosterone and they make a fair amount of it into estrogen, they might be okay, and they might not really need estrogen replacement therapy. So, we shouldn't just automatically, “Oh, you're menopausal, here's your estrogen.” We want to look into it a little bit more and understand more about the different hormones. Another hormone that is really important for us to know about, in my opinion, for women is DHEA. And that's another hormone that comes from our adrenal glands. Our body can use it to make a little bit of estrogen and testosterone. And in fact, that is where our estrogen comes from when our ovaries quit after menopause. So, depending on a woman's DHEA level, she may have relatively more or less estrogen inside her cells.
[00:58:05] And that DHEA goes down with age, but it also goes down with stress. So, if we have acute stress, it can go up, but over time it can go down. So, looking at the lay of the land amongst these different hormones can help us to understand better. And also looking at cortisol, which is our main stress hormone, because we've all got stress these days. And when our bodies react by making more and more cortisol, cortisol does a lot of things that are not good for cardiovascular disease. High stress, high cortisol makes your heart beat faster, it makes your blood pressure go up, it drives up your blood sugar. So, all of those things are hard on your heart and just wears your heart. If this is going on year after year after year. And then there are some really interesting studies that look at the risks for cardiovascular disease and cortisol metabolism. Is it okay if I kind of explain that for just a second?
Cynthia Thurlow: [00:59:02] Absolutely, I would love that.
Dr. Deb Matthew: [00:59:03] Okay, so there was a really interesting study that looked at what we call the circadian curve of cortisol. What naturally happens is in the wee hours of the morning, our cortisol level starts to go up. And cortisol is long-acting adrenaline. So, it's like we get this little adrenaline surge in the wee hours of the morning. So, our eyes pop open and we leap from bed and we're ready to start our day. And then over the day, cortisol levels start to go down. So, they're nice and low at night and we're relaxed and we can fall asleep and we sleep through the night. Now that's not what happens for a lot of people, right? For a lot of people, it gets flipped around backwards. So, in the morning they don't get that peak.
[00:59:43] So, they're exhausted and they have to press the snooze button a few times and they drag themselves out of bed. It takes them a while to get going and then at night their cortisol is higher and now they can't sleep, they're wide awake, they need an Ambien, so it gets flipped around backwards. But for some people, that up and down curve ends up being a flat line. So, they lose that circadian change that circadian rhythm. And it turns out that circadian rhythm is really, really important. So, if cortisol levels are chronically elevated throughout the day, we know that's hard on our heart because higher blood pressure and higher heart rate and etc. So that's not a good thing. But what was actually worse if it was just a flat curve? There was no up and down.
[01:00:32] The flat level of cortisol over the day had the strongest association with cardiovascular risk, stronger than high blood pressure, high cholesterol, high blood sugar, etc., and in fact they did a correlation. They showed that like how strong was the correlation between bad cholesterol and heart disease? How strong was the correlation between the systolic blood pressure, which is the top number on your blood pressure and heart disease, and then the diastolic, the bottom number on your blood pressure? They looked at all the different numbers and what they found was when they crunched the numbers and put it all together, it actually looked like the flat cortisol was the most important one out of all of them. But that is not what cardiologists are looking at.
[01:01:19] Cardiologists A, don't measure cortisol at all. But for a lot of doctors, if they were going to measure cortisol, they just do it on a blood test and you can't see the curve on a blood test or sometimes if they're looking for a tumor, they'll do a 24-hour urine, but you can't see the curve. The only way that we can see the curve is in a saliva test or a urine test where we do multiple samples over 24 hours so that we can see what's going on. So that's something that I like to look at in my patients because we see so commonly that this is a problem. This is sort of part of our modern civilization. We lose all of our circadian rhythms. We're in bright lights all the time,we've got lots of stress, we've got TV and we got our phones. Oh my gosh, we can scroll through Facebook 24/7. We're not going to bed at a decent hour. And so, our circadian rhythms are all messed up. And that's not a good thing for heart disease risk.
Cynthia Thurlow: [01:02:17] It's really interesting because I think about when I've looked at flat cortisol patterns with saliva, dry urine, and these are the people that are chronically stressed, wiped out. I mean, it could be from a variety of different reasons, but it would make sense, kind of mechanistically, that this is someone that's at greater risk. Now, I'm curious, and I'm not sure if you do this in your practice, but are you ordering CACs? Are you doing coronary artery scans, because that's one thing that, as I was diving into this research to prep for our conversation was that, women as their clinicians are considering using HRT. Who's appropriate, who is not. That five-year window is significant for plaque burden, plaque progression. And so, I was curious, are you doing the CACs and the CIMT?
[01:03:04] And obviously we'll explain what these are. These are diagnostic tests that are generally inexpensive and noninvasive, but can be very helpful navigating choices of using HRT or other modalities to address lipid abnormalities, etc.
Dr. Deb Matthew: [01:03:19] Yeah, I would say that I don't routinely as the standard order these on everybody. If somebody has a strong family history of heart disease, if they've got risk factors, I mean, if there's real reasons that we need to be concerned about cardiovascular disease risk, then we absolutely do. The coronary calcium score is basically a CAT scan of the chest. And the CAT scan can see if there's plaque in your arteries. And, there have been times when we've found people who were completely asymptomatic and they had no idea, but they actually had some pretty significant blockages in their blood vessels.
[01:03:55] And so, now that we know that, we can jump in and do the things that we need to do in order to help protect them so that they don't have a heart attack. Sometimes and frequently, we find people have no plaque showing in their arteries at all. And I think it's important to say it's not perfect because it can see the calcified kind of plaque. So, there are some kinds of plaque that won't show. But generally speaking, if they don't see any plaque, if your score is zero, that's a really good sign because if your blood vessels are going to get-- if you have atherosclerosis and you've got plaque building in your blood vessels, it doesn't start on Thursday. This has been something that's brewing for decades and continues to get worse.
[01:04:37] So, if we already see some, and it's a small amount that wouldn't preclude me from prescribing hormones, but it tells us the problem has started. We need to jump in and make sure that we can do to not make it any worse. And if it looked worrisome on the test, then definitely we would want to think about what we were doing both with hormones and everything else in order to minimize the risk. And the coronary intima media thickness is looking at the lining of the blood vessels leading to the brain. And so that's a predictor for "are you at risk for stroke?” Because do you have plaque in the blood vessels leading to the brain? So, I would say that we generally reserve them for people who, for whatever reason, were worried about them.
Cynthia Thurlow: [01:05:20] No. And it's amazing. So, for full transparency, and I've been talking more about this on social media, I have some genetic lipid issues, which now that I know as much as I do, I'm like, “Okay, I'm a hyper absorber.” I absorb too much cholesterol, so I have a high ApoB, I've got a high LDL, I've high HDL. It's kind of like this constellation of lipid issues, but it's genetically mediated. And so, I had a CAC, I had a CIMT. I had to pay out of pocket. I think between the two tests, it was $250. But to your point, if I go to have a regular CAT scan, my insurance company is going to get charged probably several thousand dollars and I'll have a high deductible.
[01:06:01] And so it's fascinating to me how the way that our insurance industry works and how they arbitrarily choose to cover some tests and not others. I'm sure that's probably a conversation for another day. So, as you're navigating cardiovascular risk, people sharing about their family history or personal history, are you looking at advanced lipid markers? Are there other labs that you're looking at to help risk stratify your patients?
Dr. Deb Matthew: [01:06:28] Absolutely. Yes, so just a regular old lipid panel is just not enough to get the information that we need. So, we want the advanced lipid panel. And what that tells us is what kind of bad cholesterol do you have and what kind of good cholesterol do you have? And the analogy for bad cholesterol that I like is you can have small particles or big particles. And if you think of the lining of your blood vessel like a tennis net, if you have small, dense particles, they're kind of like a golf ball. And if you throw the golf ball at a tennis net, it's going to go right through. So, the golf balls can get into the lining of your blood vessels and start to form plaque. If you have big fat fluffy particles, they're like a beachball.
[01:07:11] So, if you were to throw a beach ball against a tennis net, it's just going to bounce off. So, these just bounce on through your blood vessels and they really don't cause plaque. So, you can have a high LDL or high bad cholesterol number on your blood test, but if it's all these beachballs, it doesn't really significantly increase your risk for heart disease. But even if your bad cholesterol number isn't so bad, but it's really made up of mostly all of these dense golf balls, that's much more worrisome. And the same thing is true for good cholesterol. Knowing your number of good cholesterol is not enough. Because if you think of good cholesterol, the analogy is like a vacuum cleaner.
[01:07:51] So, if you have big fat good cholesterol particles or a big old shop vac that's sucking plaque out of your arteries, it's not exactly how it works. But for the analogy, you get the picture. So, you can have the big fat shop vac sucking lots of stuff out, or you can have like a little handheld dust buster that's barely sucking any out. So, you can have little wimpy good cholesterol particles that aren't very protective. So, if we know more about the size of your cholesterol particles that can give us more information about just how worried do we need to be? Because if you've got all the wrong-sized particles, even if your cholesterol is only mildly elevated, we might need to be really worried about it.
[01:08:31] And maybe one more thing about cholesterol that I think people really need to know is the number of your total cholesterol is somewhat irrelevant. I mean, unless it's 500. But generally speaking, the total cholesterol number really doesn't mean anything. Roughly, it's the good cholesterol plus the bad cholesterol added together gives your total. The math doesn't quite work. But if you have a generous amount of good cholesterol, that can drive your total cholesterol number up. But that doesn't necessarily increase your risk for cardiovascular disease. So, there's just a lot more that has to go into the analysis of cholesterol besides just what your total cholesterol number is. And at the end of the day, 50% of people who have a heart attack have completely normal cholesterol. And 50% of people who have high cholesterol never have a heart attack.
[01:09:23] So, cholesterol is really actually not one of the greatest risk markers or predictors of cardiovascular disease. And so, some of the other things that we look at is Lp (a) or lipoprotein (a), which I like to describe as like, there's good cholesterol and there's bad cholesterol, right? LDL and HDL. So, this is like nasty bad cholesterol. So, this is like bad cholesterol that's been inflamed and oxidized. It does tend to be genetic. So, it's a little bit harder for us to control with diet and exercise and whatever. But one of the things that can help to lower that lipoprotein (a) is estrogen. So, I wouldn't prescribe estrogen for the sole purpose of lowering that lipoprotein (a). But we don't like that one. And that is one that we look for.
[01:10:10] Another thing that we look for is C-reactive protein or CRP. It's just a marker of inflammation. And it doesn't tell us where the inflammation is exactly. It's not like when you twist your ankle and your ankle gets all swollen, we know the inflammation is in your ankle. It's just inflammation that's going through your bloodstream. But really heart disease is-- Inflammation is the root cause of heart disease. So, if you have a lot of inflammation, it's an important risk factor. And of course, there's so many things that we can do in order to reduce your risk. And generally speaking, hormones are anti-inflammatory. And if I can go back to cholesterol, I'll take a breath after this, I promise. But cholesterol is really not the terrible thing that we've been led to believe.
[01:10:53] Because not only just because you have high cholesterol doesn't mean you're going to have a heart attack, but cholesterol is really, really important as a building block for your brain. And so, when people have low cholesterol, they actually have greater risks for dementia. So, we're putting lots of people on cholesterol medicines and driving their cholesterol way down. And of course, if you're at high risk for having a heart disease and you could drop dead next Thursday day, we're not going to spend as much time worrying about dementia when you're 90, because we just need you to get there. But low cholesterol is not really the goal because you need cholesterol for your brain. You need cholesterol to make vitamin D, which is really a hormone. Even though we call it a vitamin, it behaves like a hormone and estrogen, progesterone, testosterone, cortisol, DHEA, all these hormones we're talking about today, they're all made out of cholesterol. And so, if your body is deficient in these hormones, one of the mechanisms is to make more cholesterol, because it's the building block to make your hormones. And if we can give you balanced hormones, the natural form of hormones, just kind of normalize things, sometimes we see the cholesterol go down.
Cynthia Thurlow: [01:12:06] It's such an important distinction because I feel that cholesterol has really gotten a bad rap and just in putting questions out across social media in the past few weeks, specific to lipids, because I've been interviewing several lipid experts. It's interesting how many people have said, “My total cholesterol is X. My HDL, LDL look good.” According to them, my physician, my NP, my PA, they'd like to put me on a statin. I was like, “This is not medical advice.” But high cholesterol is not an indication per se. It's just a mechanism for transporting things in your body, these lipoproteins. And so, it's interesting, being in cardiology for so many years, I started to back down on statins when I watched my patient’s total cholesterols go down, especially because low total cholesterol can be a marker for morbidity and mortality.
[01:13:02] And how many of my patients would have total cholesterol around 125 or 100. And I would say to them, “My goodness, you're having all these cognitive effects.” You're having all these other things that are going on. Yes, if we look at the literature and we look at evidence-based medicine because you have vascular disease, a statin is indicated, but I think this dose is way too much and so we would start backing down. And so, with that being said, I think that there's more to the lipid analysis and all those little nuances that you alluded to that can be very important. Now, when you're navigating perimenopausal, menopausal women, looking at these lipids, looking at risk stratification, considerations to HRT, are you prescribing lipid-lowering agents or do you refer on to someone else to help with those kinds of selections or is that something that you're doing in your practice?
Dr. Deb Matthew: [01:13:55] I would say that we refer people on only if they're the worst-case scenario. If we did the calcium score and we found a high score, like they're at very high risk for actually having a heart attack any day now. Definitely, we refer those kinds of people on. It's just that they're-- And I suppose to, if their cholesterol was sky high, like 500 like crazy off the charts, probably we would refer on because that's more than just poor lifestyle, habits or whatever. But otherwise, we really work hard to manage it ourselves because what we find is if we can get at the root cause for why the cholesterol is up in the first place, we can really help for it to come down.
[01:14:36] So, if we can help balance your hormones with hormone replacement therapy, if we can get your thyroid managed, because one of the important causes of high cholesterol is low thyroid. So, we see that this all the time. If somebody is mildly hypothyroid and their cholesterol is up and we optimize their thyroid hormone, their cholesterol will come down. But it should just be knee jerk. If somebody has high cholesterol, we should be checking their thyroid to make sure that's not the cause of it. But instead, we got all these women going into their doctor to say, “I can't sleep, I don't feel good, I'm exhausted, I'm gaining weight, I'm cold, I'm constipated, I got dry skin.” All the symptoms of low thyroid and they're told, your TSH is normal. That's the thyroid test. Oh, but your cholesterol is high. Here's your statin.
[01:15:22] And so that just makes no sense. So, we want to optimize hormones, we also need to optimize blood sugar because insulin resistance is a really, really important cause, not just of high cholesterol, but having the wrong type, like having the golf balls instead of the beachballs or the little shop vac, wimpy good cholesterol particles. So, if you have the wrong kind of cholesterol particles and we put you on a statin medicine, we can lower overall how much, but it doesn't really change what type you have. But if we can improve your blood sugar metabolism, that can help the bad cholesterol particles get bigger, the good cholesterol particles get bigger. So, it improves your risk stratosphere in a much better way. So, there are also some natural things that we can do to help lower cholesterol. So berberine, red yeast rice.
There are things that we can do besides statin medications or other prescription medications and if cardiovascular disease is a long-term thing, so if we just never can get it right, the medicines will still be there at the end of the day if we need to turn to them someday.
Cynthia Thurlow: [01:16:34] If you love this podcast episode, please leave a rating and review. Subscribe and tell a friend.
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